JP5727133B2 - 抗イディオタイプ抗体を得る方法 - Google Patents
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- JP5727133B2 JP5727133B2 JP2009297605A JP2009297605A JP5727133B2 JP 5727133 B2 JP5727133 B2 JP 5727133B2 JP 2009297605 A JP2009297605 A JP 2009297605A JP 2009297605 A JP2009297605 A JP 2009297605A JP 5727133 B2 JP5727133 B2 JP 5727133B2
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Description
(a)自己免疫疾患に苦しめられている1人若しくはそれ以上の患者の血清から自己抗体を精製すること;
(b)該自己抗体を固相に結合してアフィニティーマトリックスを形成すること;
(c)免疫グロブリンを含んでなるプールした血漿若しくはB細胞を該アフィニティーマトリックスと接触させ、次いで未結合の血漿成分を除去すること;
(d)自己抗体に対する抗イディオタイプ抗体(抗Id)である結合した免疫グロブリンをマトリックスから溶出すること;
(e)複数の分子メンバーを含んでなる分子ライブラリーを提供すること;ならびに
(f)該抗Idを該分子ライブラリーと接触させること、および該抗Idにより結合される結合した分子を単離すること(該結合した分子は自己抗体のあるイディオタイプを模倣する分子である)
を含んでなる、1種または複数の自己免疫疾患関連自己抗体(auto−antibody)のイディオタイプを模倣する分子の同定方法を提供する。
自己免疫疾患は自己抗原に対する細胞性および体液性応答の結果である。体液性の優勢な自己免疫状態は、それが今日そうであることが知られているにしろ将来そうしたものとして診断されうるものであるにしろ、患者自身のエピトープの1種若しくはそれ以上を結合する抗体を患者がその経過中に産生する疾患、疾病、障害若しくは症候群を包含する。
(a)自己免疫疾患に苦しめられている1人若しくはそれ以上の患者の血清から自己抗体を精製すること;
(b)該自己抗体を固相に結合してアフィニティーマトリックスを形成すること;
(c)免疫グロブリンを含んでなるプールした血漿を該アフィニティーマトリックスと接触させ、次いで未結合の血漿成分を除去すること;
(d)自己抗体に対する抗イディオタイプ抗体(抗Id)である結合した免疫グロブリンを該マトリックスから溶出すること;
(e)複数の分子メンバーを含んでなる分子ライブラリーを提供すること;ならびに
(f)該抗Idを該分子ライブラリーと接触させること、および該抗Idにより結合される結合した分子を単離すること(該結合した分子は自己抗体のイディオタイプを模倣する分子である);
(g)該結合した分子の1種若しくはそれ以上を固相に結合して第二のアフィニティーマトリックスを形成すること;
(h)免疫グロブリンを含んでなるプールした血漿を第二のアフィニティーマトリックスと接触させること、次いで未結合の血漿成分を除去すること;
(i)該第二のマトリックスから、自己抗体に対する第二の抗Idである結合した免疫グロブリンを溶出すること(第二の抗Idは自己免疫疾患の患者の血清由来のタンパク質と接触されていない)
を含んでなる、自己免疫疾患の患者の血清由来のタンパク質と接触されていない、自己抗体に対する抗Idの製造方法を提供する。
(a)本発明の既知のイディオタイプ特異性の一連の抗Idを提供すること;
(b)該自己抗体を該一連の抗Idと接触させること;および
(c)自己抗体に結合する抗Idを同定すること(結合した抗Idのイディオタイプは自己抗体のイディオタイプである)
を含んでなる、自己抗体の特異的1イディオタイプの同定方法を提供する。
(a)被験体を本発明の分子で免疫すること;
(b)該被験体から血清を収集すること;および
(c)該血清からヒト抗Id免疫グロブリンを精製すること
を含んでなる、精製されたヒト抗Id免疫グロブリンの製造方法を提供する。
自己免疫−a−aのイディオタイプを模倣する分子の同定方法の一態様を図1に具体的に説明する。
自己抗体に対する抗Idの製造方法の一態様を図2に示す。
1種の自己抗体のイディオタイプを模倣する分子の同定
1.材料および方法
実施例Iで上述されたところのIVIGから単離した抗−抗dsDNA(抗Id)を使用して、M13ファージにより提示される特異的ペプチドを検出した。商業的Ph.D.7TMファージディスプレイライブラリー(カタログ番号E8100S、New England Biolabs Inc)を、発明者により以下のとおりわずかに改変した製造元の手順に従って使用した:
50mM NaHCO3(Ph8.5)中の抗Idを、スルホ−NHS−LC−ビオチン(Pierce #21335)を添加することによりビオチニル化し、氷上で2時間インキュベートしかつ2%麦芽糖に対し透析した。ビオチニル化の効率はニュートラビジン(neutravidine)被覆プレート上でのELISAによりアッセイした。
ペプチドへの抗Idの結合をELISAにより試験した。
以下のペプチドを使用した:
上と同一のプロトコルを使用したが、しかしこの試験で使用したペプチドは、前の実験で最初のペプチドであるペプチド番号1を除き文献から採用した。
上の2節(「合成ペプチドへの抗Idの直接結合」)で示した15種の環状ペプチドの混合物を使用して、7例の狼瘡患者のそれぞれからアフィニティー精製した抗dsDNA抗体への抗Idの結合を阻害した。混合物は狼瘡患者の抗dsDNA Id(1種若しくは複数)の認識確率を増大させるよう作成した。
1.緒言:
本実施例は、共通のSLEイディオタイプすなわちId 16/6の同定をもたらした慣習的方法での直接選択の実験的立証を提供する。16.6 CDR、CDR3に基づくペプチドの1種がマウスでSLEの症状を引き起こし得る一方、CDR1の優勢な(predominate)機能は実験的SLEマウス(1)において疾患を軽減することであることが判明している。
2.1 合成ペプチド。
706と呼称される16.6モノクローナル抗体CDR1に基づくペプチドTGYYMQWVKQSPEKSLEWIG(pCDR1)および707と呼称されるCDR3に基づくペプチドYYCARFLWEPYAMDYWGQGS(pCDR3)を、t−ブチルオキシカルボニル(BOC)戦略のための会社のプロトコルを使用して、自動化合成機(Applied Biosystemモデル430A)で製造した(Kent、前掲書、Schnolzer,M,、Alewood,P.F.とKent,S.B.H.(1992)Int.J.Pept.Protein Res.40、180−193)。R706と呼称される逆順のCDR1、GIWELSKEPSQKVWQMYYGTを対照として使用した。別の類似の合成において、生じるペプチドを、後にELISA試験で使用するためにそれらのN末端でビオチンにより標識した。
2.2.1 還元的アミノ化によるペプチド707のカップリング
2.2.1.1 活性化プロトコル
a.過ヨウ素酸酸化可能なマトリックスの創製
10mlのトヨパール(Toyopearl)NH65F(Tosohass、日本)を焼結グラスフィルター(多孔性G3)上で300mlの水で洗浄し、次いで1M NaOHで5回連続して(合計80ml)洗浄した。樹脂を焼結グラスフィルターから取り出し、そして10mlの1M NaOH、1mlのグリシドール(Sigma)および0.01gのホウ水素化ナトリウム(NaBH4)で懸濁した。反応混合物を穏やかな回転を伴い室温で一夜インキュベートした。朝に、樹脂を200mlの水、1M NaClおよび再度水のそれぞれで徹底的に洗浄した。グリシドール修飾樹脂は今や過ヨウ素酸酸化の準備ができた。
b.マトリックスの直接過ヨウ素酸酸化
過ヨウ素酸酸化樹脂を調製するために以下のプロトコルを設計した。すなわち、ビシナルヒドロキシル基を含有する10mlの水分を含むゲルを10mlの0.2M NaIO4(100mlの水中の4.28gのメタ過ヨウ素酸ナトリウム)に再懸濁し、そして穏やかな回転により十分に混合した。反応を室温で90分間継続した。ホルミル樹脂を300mlの水により洗浄して酸化を停止した。この手順により創製されるアルデヒドは、カップリング能力の低下を伴わずに樹脂が長期間保存されることを可能にするのに十分安定である。
NaCNBH4および特定のペプチドを含有する1mlのリン酸緩衝液、pH7.0を2mlの過ヨウ素酸酸化マトリックスに添加した。リン酸緩衝液中のペプチドの濃度は10mg/ml(約3.3μモル/ml)であった。従って、該比は1mlの樹脂に対し1.1μモルの707であった。反応を攪拌しながら室温で一夜継続した。カップリングした樹脂を水、1M NaClおよび再度水で徹底的に洗浄して、未反応のリガンドおよびシアノホウ水素化ナトリウムを除去した。
2.2.2 CNBr活性化マトリックスへのペプチド706のカップリング
3gの凍結乾燥したCNBr活性化セファロース(Sepharose)4ファストフロー(fast flow)を20mlの1mM HCl(氷冷)に懸濁した。樹脂を200mlの酸を使用して焼結グラスフィルター(多孔性G3)上で15分間激しく洗浄した。最終洗浄後に、2mlの洗浄した樹脂を、カップリングされるべきペプチドを溶解しておいたカップリング溶液中に移した。カップリング溶液は900μlの0.1−M炭酸ナトリウム(NaHCO3)、pH8.5および100μlの100mg/mlのペプチド706を含有した。樹脂に対するペプチドの比は再度1mlの樹脂あたり1.1μモルであった。混合物を4℃で一夜回転した。カップリング後、樹脂を含むバイアルを樹脂の沈降のため垂直位置で放置した。上清を廃棄し、そして、樹脂上の残存する活性基の封鎖のため15mlの0.2Mグリシン、pH8.0を添加した。封鎖は回転しながら室温で4.5時間実施した。
2.3 アフィニティークロマトグラフィー:ペプチドカラムを使用する静脈内免疫グロブリン溶液からの抗イディオタイプの精製。
ペプチドカラム溶出物(706および707)の結合効率を測定するために以下のELISAを実施した:
マイクロタイタープレート(Coster、米国)を、0.1M、pH8.8の炭酸−重炭酸緩衝液(Sigma 米国)に懸濁した10μg/mlのニュートラビジン(NeutrAvidin)(Pierce、米国)で2〜8℃で一夜被覆した。被覆溶液を除去し、洗浄緩衝液(1×PBS)で3回洗浄し、そしてウェルあたり200μlのブロッキング溶液(新たに調製した1%I Block、Tropix、米国)を添加しかつ37℃で1時間インキュベートした。被覆しかつブロッキングしたプレートは使用前に1か月間−20℃で保存し得る。
200mlのIVIGを2mlのペプチドカラム(一方はCNBr活性化セファロース(Sepharose)マトリックスに結合するペプチド706、および他方は還元的アミノ化によりポリマーマトリックスに結合する707ペプチドよりなる(材料および方法を参照されたい))のそれぞれに負荷した。
Claims (1)
- (1) KHETTET
(2) PPNHSHL
(3) AGLKNSQ
(4) ASTIRAG
(5) VRVLLRS
(6) TQPPELP
(7) LSQPERW
(8) PPPDLHA
(9) GTTQWVL
(10) YGTPSSE
(11) SLQRHPW
(12) PLPDWRV
(13) DWLYSRS
(14) PPQKHLL
(15) KYKRKYP
またはその組み合わせから選択されるヘプタペプチドが固相マトリックスに結合した、全身性エリテマトーデス(SLE)抗イディオタイプ抗体を結合するための固相マトリックス。
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EP2258727A1 (en) | 2009-05-27 | 2010-12-08 | Wezen Biopharmaceuticals S.r.l. A Socio Unico | Immunoglobulin preparation for the treatment of autoimmune diseases and immune system disorders |
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JP2014504594A (ja) * | 2011-01-10 | 2014-02-24 | オプコ ファーマシューティカルズ、エルエルシー | 自己免疫疾患における抗原代用物 |
US20140088017A1 (en) | 2011-05-23 | 2014-03-27 | Yeda Research And Development Co., Ltd. | Use of akt phosphorylation as a biomarker for prognosing neurodegenerative diseases and treating same |
US10131709B2 (en) | 2011-12-28 | 2018-11-20 | Immunoqure Ag | Nucleic acid molecules encoding monoclonal antibodies specific for IL-22 |
WO2013098419A1 (en) | 2011-12-28 | 2013-07-04 | Immunoqure Ag | Method of providing monoclonal auto-antibodies with desired specificity |
EP2880168B1 (en) * | 2012-08-05 | 2017-01-11 | Absci, LLC | Inducible coexpression system |
WO2015001013A2 (en) | 2013-07-03 | 2015-01-08 | Immunoqure Ag | Human anti-ifn-alpha antibodies |
EP4015539A1 (en) * | 2020-12-16 | 2022-06-22 | Cryolab S.r.l. | Method for producing human monoclonal anti-idiotype antibodies |
CN116731184A (zh) * | 2022-11-25 | 2023-09-12 | 厦门康基生物科技有限公司 | 一种特异性结合Taq酶的单克隆抗体F6H12及其应用 |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4690905A (en) * | 1983-11-16 | 1987-09-01 | Albert Einstein College Of Medicine Of Yeshiva University, A Division Of Yeshiva University | Method for removal of human antibodies to native DNA from serum |
CA1256795A (en) * | 1983-12-28 | 1989-07-04 | Dennis A. Carson | Anti-idiotype antibodies induced by synthetic polypeptides |
US5068177A (en) * | 1983-12-28 | 1991-11-26 | Scripps Clinic And Research Foundation | Anti-idiotype antibodies induced by synthetic polypeptides |
US6270771B1 (en) * | 1988-10-06 | 2001-08-07 | Institut Pasteur | Peptide sequences specific for the hepatic stages of P. falciparum bearing epitopes capable of stimulating the T lymphocytes |
FR2672290B1 (fr) * | 1991-02-05 | 1995-04-21 | Pasteur Institut | Sequences peptidiques specifiques des stades hepatiques de p. falciparum porteuses d'epitopes capables de stimuler les lymphocytes t. |
US5882879A (en) * | 1990-02-28 | 1999-03-16 | Gist-Brocades, N.V. | Method for influencing β-lactam antibiotic production and for isolation of large quantities of ACV synthetase |
US6864060B1 (en) * | 1993-03-31 | 2005-03-08 | Cadus Technologies, Inc. | Yeast cells expressing modified G proteins and methods of use therefor |
IL113159A0 (en) | 1995-03-28 | 1995-06-29 | Yeda Res & Dev | Synthetic peptides and pharmaceutical compositions comprising them |
AU4503497A (en) * | 1996-09-26 | 1998-04-17 | Leinwand, Leslie A. | Transgenic model for heart failure |
WO1998026086A1 (en) * | 1996-12-11 | 1998-06-18 | University Of Florida | Novel methods and compositions for treatment of autoimmune diseases |
US6183997B1 (en) * | 1997-03-21 | 2001-02-06 | Stratagene | Polymerase enhancing factor (PEF) extracts PEF protein complexes isolated PEF proteins and methods for purifying and identifying same |
US7041490B1 (en) * | 1997-11-28 | 2006-05-09 | Serono Genetics Institute, S.A. | Chlamydia trachomatis polynucleotides and vectors, recombinant host cells, DNA chips or kits containing the same |
US6551795B1 (en) * | 1998-02-18 | 2003-04-22 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to pseudomonas aeruginosa for diagnostics and therapeutics |
US7504490B1 (en) * | 1998-10-16 | 2009-03-17 | Oscient Pharmaceuticals Corporation | Nucleic acid and amino acid sequences relating to Apergillus fumigatus for diagnostics and therapeutics |
WO2001064835A2 (en) * | 2000-02-28 | 2001-09-07 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
US20080229439A1 (en) * | 1999-05-06 | 2008-09-18 | La Rosa Thomas J | Nucleic acid molecules and other molecules associated with transcription in plants and uses thereof for plant improvement |
US20100293669A2 (en) * | 1999-05-06 | 2010-11-18 | Jingdong Liu | Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
WO2000069898A2 (en) * | 1999-05-14 | 2000-11-23 | Arbor Vita Corporation | Molecular interactions in allergy cells |
US20050037969A1 (en) * | 1999-05-14 | 2005-02-17 | Arbor Vita Corporation | Molecular interactions in hematopoietic cells |
EP1224223A4 (en) * | 1999-09-24 | 2004-08-11 | Univ Monash | IMMUNO-INTERACTIVE MOLECULE AND ITS APPLICATIONS IN THE TREATMENT OF SUBJECTS WITH ALLERGY TO HEV B 5 |
PL361223A1 (en) * | 1999-12-30 | 2004-09-20 | Aplagen Gmbh | Method for identifying substances which mimic mammal epitopes |
CA2407352A1 (en) * | 2000-04-21 | 2001-11-01 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of acne vulgaris |
AU2001271839A1 (en) * | 2000-07-05 | 2002-01-14 | Pharmacia And Upjohn Company | Human ion channels |
US6569431B2 (en) * | 2000-10-17 | 2003-05-27 | The Regents Of The University Of California | Recombinant antibody fragments as autoantibody antagonists |
CA2423843A1 (en) | 2000-10-18 | 2002-04-25 | Sloan-Kettering Institute For Cancer Research | Uses of monoclonal antibody 8h9 |
CA2881568C (en) * | 2000-10-27 | 2019-09-24 | Novartis Vaccines And Diagnostics, Inc. | Nucleic acids and proteins from streptococcus groups a & b |
US7214786B2 (en) * | 2000-12-14 | 2007-05-08 | Kovalic David K | Nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
WO2002079449A2 (en) * | 2001-03-28 | 2002-10-10 | Incyte Genomics, Inc. | Molecules for disease detection and treatment |
US7335467B2 (en) * | 2001-05-15 | 2008-02-26 | Ludwig Institute For Cancer Research | Breast cancer antigens |
US20030235833A1 (en) * | 2001-06-18 | 2003-12-25 | National Institute Of Advanced Industrial Science And Technology | Guanosine triphosphate-binding protein coupled receptors |
WO2003099868A2 (en) * | 2002-05-28 | 2003-12-04 | Omrix Biopharmaceuticals Inc. | Method for obtaining anti-idiotype antibodies |
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JP4489582B2 (ja) | 2010-06-23 |
EP1511772A2 (en) | 2005-03-09 |
WO2003099868A3 (en) | 2004-01-15 |
WO2003099868A2 (en) | 2003-12-04 |
US8450067B2 (en) | 2013-05-28 |
AU2003228084A1 (en) | 2003-12-12 |
US20130244925A1 (en) | 2013-09-19 |
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